Acetalins (acetyl plus enkephalin) are opioid receptor antagonists determined through the use of synthetic peptide combinatorial libraries that are made up of more than fifty million hexapeptides. A synthetic peptide combinational library was screened in search of compounds able to displace tritiated encephalin from u opioid receptor binding sites in crude rat brain homogenates. The structure of hexapetide is characterized by an acetyl group at the N-terminus and an amide group on the C-terminus. In 1993, Dooley and his colleagues first termed a class of opioid receptor ligands as acetalins with the sequence Ac-RFMWMK-NH2. Acetalins were identified as potent u receptor antagonists in the guinea pig ileum assay with high affinity for μ and κ3 opioid receptors. In the mouse vas deferens assay, acetalins were found to be relatively weak antagonists because of low affinity for δ receptors, weak affinity for κ1 receptors, and no affinity for κ2 receptors.

Mechanism of action

The opioid receptors, for encephalin, are produced by the body. Acetalins belong to G-protein-coupled receptor family with other opioids as ligands as well, such as dynorphins, endorphins, endomorphins. In a mammalian parasympathetic ganglion, enkephalian exerts function by blocking ganglionic transmission by both pre- and post-synaptic actions. It is believed that acetalins are responsible for the rate of neurotransmitter release through their inhibitory for this release. Thus, the use of opiates can enhance the effects of these inhibitory mechanisms. Then the exogenous opiates will mainly control the rate of neurotransmitter release instead of endogenous enkephalin.

Application of acetalin

Acetalins act as analgesics and sedatives in the body. Endorphins produced by nerve endings of the central nervous system and the adrenal medulla seem to have influence on mood and motivation. The brain also releases endorphins and enkephalins, blocking pain signals in the spinal cord and these morphine-like substances. Therefore, acetalins are closely related to mood and activation. Enkephalins and endorphins are able to be used as natural killer.